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Stress Isn't Bad Just for Ewe

NEW ORLEANS, LOUISIANA--Pregnant sheep given a natural stress hormone are more likely to have offspring that end up with high blood pressure, according to researchers in sheep-laden Australia. On 21 April at a meeting of the Federation of American Societies for Experimental Biology here, the team also reported that the stress hormone can alter the development of the lambs' kidneys, which play an important role in regulating blood pressure. Although it's too early to extrapolate the findings to humans, the study suggests that stress early in pregnancy may affect fetuses.

Research in recent years has suggested that unfavorable conditions in the womb, such as malnutrition, can harm the developing fetus as well as the adult it grows up to be. Many such correlations have been proposed in humans, but proving that the fetal environment directly affects adult health has been difficult. So fetal physiologist Marelyn Wintour and her colleagues at the University of Melbourne turned to sheep to determine whether maternal stress could harm offspring later in life.

The group gave cortisol--a hormone the body produces when under stress--to pregnant sheep less than a month into their 5-month pregnancy. The amount given, says Wintour, approximates that produced in humans by a significant stress, such as job loss. The offspring of these sheep exhibited high blood pressure 5 months after birth and sustained it for up to 7 years. The result was more pronounced among male offspring. However, the offspring of sheep given cortisol two and a half months into their pregnancies and another group given saline did not have high blood pressure.

Cortisol caused changes in expression of genes in the brain and the kidneys of fetal sheep, the team found. And the animals had only 60% as many nephrons, the functional units of the kidney, as did normal lambs. Somehow, says Wintour, cortisol derails development of the kidneys, interfering with the animals' regulation of salt and water--and blood pressure.

"It's excellent," says Jeff Schwartz of the University of Adelaide, Australia. He's particularly intrigued that the cortisol made its way to the fetus despite the fact that the placenta is designed to keep it out. It's too soon to say how the work might apply to people, he adds, noting that the infusions of cortisol were so early that, on the human timeline, a woman might not yet know she's pregnant.